The goal of the Phase I research is to develop ex vivo gene therapy that will achieve long-term, localized delivery of human neurotrophin-3 (hNT-3) in the rat contusion model of spinal cord injury. Our overall goal is to develop cell-based delivery of neurotrophins and other proteins as therapy for acute spinal cord injury. The following are the Phase I specific aims: Aim 1: To test functional recovery in response to NT-3 in rat spinal cord injury model. Aim 2: To test the effect of methylprednisotone on NT-3 based recovery of injured rats. In Phase II research we will develop a stereotaxic injection method to introduce cells into the injured spinal cords of rats, and study the effect of delaying implantation (24 to 48 hours post-injury) on cell survival, protein production, and functional recovery. Besides NT-3, we also will transduce cells with virus that produces brain-derived neurotrophic factor (BDNF), and look at its effect alone and in combination with NT-3 on functional recovery in animal models. Based on the results in Phase I we will continue working with methylprednisolone. We will test the system in a primate model, and develop human cells towards beginning Phase I clinical trials. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE